Difference between revisions of "Phosphatase Subfamily PGP"

Revision as of 01:16, 22 March 2015

Phosphatase Classification: Fold HAD: Superfamily HAD: Family NagD: Subfamily PGP

PGP is ubiquitous in eukaryotes. The two members in human have distinct functions: PDXP (aka chronophin) dephosphorylates protein cofilin on serine residue, as well as pyridoxal 5'-phosphate; PGP is a putative tyrosine-specific protein phosphatase. PDXP is mainly expressed in brain; PGP is widely expressed in different tissues.

Evolution

The PGP subfamily is extremely conserved in eukaryotes, rarely absent from eukaryotic genomes. Human has two members of this subfamily: PGP and PDXP. PGP has obvious orthologs in vertebrate, but PDXP has obvious orthologs in coelacanth, birds, eutheria, rodents and primates. Thus, human PGP and PDXP has a deep root in eukaryotes but probably diverged from ancestral gene in function in early vertebrates.

Domain

The PGP subfamily has a single domain: HAD domain.

Function

PDXP (Chronophin) is abundantly expressed in brain [1] (see also GTEx RNA-seq data). PDXP has two distinct substrates.

• Pyridoxal 5'-phosphate. PDXP was first identified as pyridoxal phosphatase, which catalyzes the dephosphorylation of pyridoxal 5'-phosphate (PLP) and pyridoxine 5'-phosphate. PLP is the active form of vitamin B6 that acts as a coenzyme in maintaining biochemical homeostasis [1, 2, 3].

• Protein cofilin. PDXP dephosphorylates cofilin at serine, therefore regulating assembly and disassembly of actin filaments [4, 5, 6]. It is worthy pointing out that another phosphatse subfamily, slingshot, also dephosphorylates cofilin.

In contrast with PDXP, PGP (AUM) is widely expressed in different tissues (see also GTEx RNA-seq data). PGP is a putative tyrosine-specific phosphatase [7], but its physiological substrate needs to be found.

References

1. Jang YM, Kim DW, Kang TC, Won MH, Baek NI, Moon BJ, Choi SY, and Kwon OS. Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. J Biol Chem. 2003 Dec 12;278(50):50040-6. DOI:10.1074/jbc.M309619200 | PubMed ID:14522954 | HubMed [Jang03]
2. Gao G and Fonda ML. Identification of an essential cysteine residue in pyridoxal phosphatase from human erythrocytes. J Biol Chem. 1994 Mar 18;269(11):8234-9. PubMed ID:8132548 | HubMed [Gao94]
3. Kim DW, Eum WS, Choi HS, Kim SY, An JJ, Lee SH, Sohn EJ, Hwang SI, Kwon OS, Kang TC, Won MH, Cho SW, Lee KS, Park J, and Choi SY. Human brain pyridoxal-5'-phosphate phosphatase: production and characterization of monoclonal antibodies. J Biochem Mol Biol. 2005 Nov 30;38(6):703-8. DOI:10.5483/bmbrep.2005.38.6.703 | PubMed ID:16336786 | HubMed [Kim05]
4. Gohla A, Birkenfeld J, and Bokoch GM. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol. 2005 Jan;7(1):21-9. DOI:10.1038/ncb1201 | PubMed ID:15580268 | HubMed [Gohla05]
5. Huang TY, Minamide LS, Bamburg JR, and Bokoch GM. Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation. Dev Cell. 2008 Nov;15(5):691-703. DOI:10.1016/j.devcel.2008.09.017 | PubMed ID:19000834 | HubMed [Huang08]
6. Kestler C, Knobloch G, Tessmer I, Jeanclos E, Schindelin H, and Gohla A. Chronophin dimerization is required for proper positioning of its substrate specificity loop. J Biol Chem. 2014 Jan 31;289(5):3094-103. DOI:10.1074/jbc.M113.536482 | PubMed ID:24338687 | HubMed [Kestler14]
7. Seifried A, Knobloch G, Duraphe PS, Segerer G, Manhard J, Schindelin H, Schultz J, and Gohla A. Evolutionary and structural analyses of mammalian haloacid dehalogenase-type phosphatases AUM and chronophin provide insight into the basis of their different substrate specificities. J Biol Chem. 2014 Feb 7;289(6):3416-31. DOI:10.1074/jbc.M113.503359 | PubMed ID:24338473 | HubMed [Seifried14]